UC Santa Barbara

The treatment of disease is unarguably one of the most important applications of the emerging field of bioengineering, which seeks to apply engineering principles to biological challenges. In the field of medicine, bioengineers have played a role in a multitude of areas including diagnostics, monitoring and therapy, working with scientists and physicians to develop imaging equipment, biocompatible implants, and targeted cancer therapies. These advances often used materials that a few decades ago would have been unheard of in healthcare application, such as titanium, polymers and nanoparticles. In keeping with this pioneering spirit, my research sought to use bioengineering applications to address the areas of diagnosis and treatment of disease. I chose Type 1 diabetes (T1D) as a model disease for this work, as challenges exist in both areas. For T1D patients taking exogenous insulin, alternatives to injection therapy could reduce the stress of daily multiple injections, increase adherence to dosing regimens and lower the incidence of skin infections. In addition, early diagnosis of T1D can provide earlier intervention, providing an opportunity for the development of therapies to slow beta cell destruction and prolong endogenous insulin production.

In the first part of this work, we demonstrate the potential of ionic liquids as both antimicrobials and drug delivery vehicles. Probably best known as “green” solvents in the chemical industry, ionic liquids are sparking interest in healthcare due to their innate antimicrobial qualities and excellent drug solvation properties. These characteristics and properties can be both finely tuned and widely modulated by changes in ion type, ratio and ion structure, providing an almost unlimited design framework. To demonstrate this, we studied how the simplest tuning parameter, ion ratio, affects both antibacterial efficacy and transdermal drug delivery of a variety of proteins including insulin. We also sought to investigate the breadth of ionic liquids in drug delivery by showing their potential to effect oral delivery of insulin. Using a combination of in silico, in vitro, ex vivo and in vivo models, we showed that a choline and geranic acid (CAGE) ionic liquid is a highly effective bactericide as well as an enhancer of transdermal and intestinal protein delivery.

In the second portion of the work, we investigate the use of bacterial peptide display libraries and next generation sequencing (NGS) in two ways; to improve epitope mapping and to search for new humoral biomarkers in T1D. We were able to demonstrate that NGS data can improve the results from PepSurf, a web-based epitope mapping program.

Finally, by profiling the antibody repertoire of plasma from T1D and non-T1D matched controls, we discovered several peptide motifs with good (30-50%) sensitivity and 100% specificity. Challenging these motifs to a larger control population of 238 assumed non-T1D samples resulted in one motif with moderate (20%) sensitivity and >99% specificity. Further development and maturation of these motifs could provide new biomarkers for T1D.